Epstein-Barr virus (EBV) is human gamma herpesvirus in the lymphocryptovirus (LCV) genera and is associated with several types of lymphoid and epithelial cell malignancies. Closely related oncogenic LCV are known to naturally infect Old World nonhuman primate species. However, it was believed that LCV did not naturally infect New World primates and were restricted to humans and Old World primates. We have recently isolated a new herpesvirus, CaIHV-3 (Callithrix herpesvirus 3), from spontaneous B cell lymphomas arising in common marmosets (Callithrix jacchus), a New Wofid primate. Like EBV, Ca1HV-3 infection can immortalize B cells in tissue culture and is persistently endemic in the adult population. We have cloned and sequenced more than 125,000 bp of the genome and have definitively identified it as the first member of the EBV-related LCV genera found in New World primates. Significant differences in the repertoire of lytic and latent infection genes in Ca1HV-3 as compared to EBV and other Old World LCV provide new opportunities for studying the molecular pathogenesis and oncogenesis associated with LCV infection. The occurrence of spontaneous lymphomas in immunocompetent animals is a unique and potentially valuable animal model system for studying LCV-induced malignancies. We will utilize the biologic similarities and genetic differences that have evolved among the human, New World, and Old World LCV to better understand EBV infection and pathogenesis in humans. Specific Aim #1. Complete the Ca1HV-3 primary nucleotide sequence. Specific Aim #2. Functional, biochemical, and genetic analyses of the Ca1HV-3 C3 gene, a positional homologue for the three EBNA-3 genes. Specific aim #3. Study the disease association, epidemiology, and evolution of New World LCV. Specific aim #4. Develop an experimental Ca1HV-3 animal model to study the pathogenesis of persistent infection and virus-induced oncogenesis.